1. Field of the Invention
The present invention is directed to nutraceutical compositions which support physical performance, attenuate muscle fatigue, and enhance aerobic respiration utilization capacity. The composition may be prepared in the form of a ready-to-drink liquid composition, or a liquid concentrate or a tablet, granulate, powder, or other solid form to be added to water or other fluid to form a drinkable liquid at the time of ingestion. Advantageously, the inventive composition enhances physiologically vital energy stores and the bio-availability of adenosine triphosphate (ATP) energy reserves. The composition also provides for regeneration of ATP in skeletal muscle, enhances the delivery and uptake of glucose in skeletal muscle, and provides essential electrolytes and other ingredients to a consumer of the liquid composition.
More specifically, the present invention relates to a novel composition comprising, consisting of, or consisting essentially of ribose, a saccharide, ATP, coenzyme Q10, caffeine, and D-pinitol. The composition may also contain minerals and electrolytes to stimulate and enhance generation of ATP activity in the body.
2. Description of the Related Art
The human body derives energy from carbohydrates, fats and proteins during chemical processes within the cells. The energy released from these nutrients is used to form the nucleotide ATP. ATP is used to promote three major categories of cellular function: membrane transport, synthesis of chemical compounds, and mechanical work. As cells use ATP to perform work, the ATP is chemically broken down into a pool of nucleotides, most of which are re-aminated and re-phosphorylated back to ATP. When intense exercise is repeated frequently, as in training, there is an accumulated loss of nucleotides from the muscle. The restoration of the nucleotide pool occurs mainly through de novo synthesis but also through the re-use of intracellular purines through the purine salvage pathway.
Carbohydrates are the primary source of energy in human diets. Essentially all carbohydrates are converted into glucose before they reach the cell. Once glucose enters the cell, enzymes in the cytoplasm or the nucleoplasm convert the glucose into pyruvic acid through a process called glycolysis. This process produces a small amount of ATP, while 90 percent of ATP is formed in the mitochondria. Pyruvic acid and acetoacetic acid (from fatty and amino acids) are converted into acetyl coenzyme-A in the cytoplasm and transported into the mitochondrion. Here a series of enzymes act upon acetyl coenzyme-A, which undergoes dissolution through a sequence of chemical reactions known as the tricarboxylic acid cycle or Krebs cycle. As a result of these processes, one molecule of glucose forms a total of 38 molecules of ATP.
Low blood glucose or muscle glycogen levels during exercise contribute to fatigue. Maintaining or elevating body carbohydrate reserves may optimize exercise performance. Pre-exercise carbohydrate consumption has the potential to increase liver and muscle glycogen concentrations during the hours before exercise. Further, carbohydrates consumed prior to exercise may be absorbed via the small intestine during exercise and help maintain adequate blood glucose concentrations. Studies have shown a 15% increase in performance and a 13% improved endurance time to exhaustion with pre-exercise carbohydrate consumption. In some studies using carbohydrate solutions containing 200 g glucose per liter, performance was improved. Carbohydrate availability during exercise was greater and the pre-exercise carbohydrate consumption increased carbohydrate oxidation above normal amounts, thereby allowing a higher work rate during the later stages of exercise.
ATP is vital to cellular function. Energy from ATP is required for membrane transport of glucose and other essential substances, such as sodium ions, potassium ions, calcium ions, phosphate ions, chloride ions, urate ions, hydrogen ions, and many other substances. Membrane transport is so important to cellular function that some cells utilize nearly half the ATP formed in the cells for this purpose alone.
ATP also supplies the energy to promote synthesis of a great number of substances, including proteins, phospholipids, cholesterol, purines, and pyrimidines. Synthesis of almost any chemical compound requires energy. For example, in the formation of one molecule of protein, many thousands of ATP molecules are broken down to release energy. Cells utilize up to 75 percent of all the ATP formed in the cell to synthesize new chemical compounds, particularly during the growth phase of a cell.
ATP is also essential for muscle contraction. In skeletal muscle, calcium ions bind to the troponin complex, causing the tropomyosin to shift and thereby expose the myosin binding sites of the actin to the myosin heads. The myosin heads move the thin filament contracting the muscle, also called a power stroke. ATP provides the energy required for the myosin heads to release the actin and move back into place for another power stroke. The amount of ATP that is present in the muscle fiber is sufficient to maintain full contraction for less than one second. The ATP is broken down into adensosine diphosphate (ADP), which is rephosphorylated to form new ATP within a fraction of a second. The two main sources of energy to reconstitute ATP are foodstuffs, such as carbohydrates, fats and proteins, and creatine phosphate.
ATP exists both inside (intracellular) and outside (extracellular) virtually every cell of the body. The role of intracellular ATP has been well established. It is largely responsible for the energetics, function and survival of cells. When the phosphate bonds of ATP are broken down, the energy released helps to empower all body functions to occur. Extracellular ATP regulates many physiological responses, such as vascular, cardiac and muscle functions, by interacting with specific ATP receptors on cell surfaces. When intracellular ATP becomes depleted, extracellular ATP can cross into cells via its catabolic components, adenosine and inorganic phosphate.
Physical activity, specifically high-intensity or prolonged exercise, requires a high rate of ATP utilization as well as a rapid rate of regeneration. The regeneration rate exceeds the maximum capacity of the muscle, resulting in the accumulation of ADP and adenosine monophosphate (AMP) in the muscle. With further adenine nucleotide degradation, inosine monophosphate (IMP) forms and accumulates in the muscle. A fraction of IMP is further degraded to nucleotide bases that are released into the bloodstream, resulting in a decrease in total adenine nucleotides (TAN, ATP+ADP+AMP) contributing to an overall decrease in ATP.
A single period of exhaustive exercise of short duration can cause ATP levels in human skeletal muscle to drop temporarily to 60-70% of resting values, but ATP levels are restored to pre-exercise levels shortly after the exercise is ended. However, the loss of nucleotides from frequently-repeated exercise exceeds the rate of regeneration, causing ATP levels to remain below baseline levels. Studies have shown that intense exercise performed regularly over one to several weeks decreases concentrations of ATP resting levels by 15-20%.
Extracellular ATP is a major regulator of vascular, cardiac and muscle functions. By activating specific ATP receptors present on vascular endothelial cells (the cells that line the blood vessels walls), ATP improves blood vessel tone and increases vasodilation, which reduces pulmonary and systemic vascular resistance (the resistance of the vessels to blood flow). These actions stimulate blood flow to peripheral areas without affecting blood pressure or heart rate. Additionally, exogenous ATP enhances the delivery of glucose, nutrients and oxygen to working and recovering muscles as well as helping to remove catabolic waste products. These mechanisms improve physical performance, benefit muscle growth, strength and recovery, and increase overall energy levels. Increases in extracellular ATP have also been demonstrated to enhance cerebral blood flow and metabolism, thereby supporting mental acuity and potentially lessening the perception of fatigue and/or exercise-associated pain.
After ingestion, ATP is broken down into adenosine and inorganic phosphate. Following rapid absorption by the gut, these compounds are incorporated into and expand the body's liver ATP pools. Detailed experimental animal studies have demonstrated that the turnover of the expanded liver ATP pools supply the necessary precursor, adenosine, for red blood cell ATP synthesis. In sum, exogenously administered ATP elevates liver ATP pools, which in turn yields elevated red blood cell ATP pools. Subsequently, the expanded red blood cell ATP pools are slowly released into the blood plasma (extracellular). Animal and human studies have both conclusively shown that oral administration of ATP elevates ATP levels in liver, red blood cells and blood plasma.
Each molecule of ATP consists of three phosphate groups and one adenosine molecule, which itself is composed of an adenine ring and a ribose molecule. Ribose is a pentose sugar found in many essential biological molecules, such as all nucleotides, nucleotide coenzymes, all forms of RNA, and ATP. Ribose is a key component and a limiting factor in the creation and regeneration of ATP. Ribose supplementation in rats has been shown to increase nucleotide salvage three- to six-fold and hypoxanthine salvage six- to eight-fold, depending on muscle fiber type. Ribose supplementation in humans has also been shown to attenuate loss of TAN during chronic high-intensity exercise, and return TAN and ATP levels to baseline within 65 to 72 hours. In contrast, subjects without ribose supplementation remained at under 80% of resting TAN and ATP levels. When consumed orally, 88-100% of ribose is absorbed in the intestines within two hours.
Coenzyme Q10 (CoQ10), like ribose, exists in all cells and is integral to many vital biological activities. Such activities include a role as an essential antioxidant, supporting the regeneration of other antioxidants, influencing the stability, fluidity and permeability of membranes, stimulating cell growth, and inhibiting cell death. Additionally, CoQ10 has a fundamental role in cellular bioenergetics as a cofactor in the mitochondrial electron transport chain (respiratory chain), and is therefore essential for the production of ATP. The human body can synthesize CoQ10 as well as derive it from several food products, including meat, fish, peanuts and broccoli. The dietary intake of CoQ10 is about 2-5 mg per day, while the total amount of CoQ10 in the body of a normal adult is estimated to be approximately 0.5-1.5 g. Studies have shown that the uptake of CoQ10 into the blood is approximately 5 to 10% of the dose administered. Dosages of 90 to 150 mg/day have shown to increase plasma concentrations by 180%. Under certain conditions including oxidative stress, production of CoQ10 may not meet the body's demand. In several medical studies and studies of trained athletes, CoQ10 supplementation has been shown to provide enhanced cellular energy levels in cardiac performance by increasing respiratory chain activity, improving oxygen utilization during exercise, accelerating post-exercise recovery, decreasing heart rate during exercise, improving performance, and increasing mean power (the average rate at which work is performed or energy is converted). CoQ10 has also been used as a supplementary treatment for diseases such as Chronic Heart Failure (CHF), muscular dystrophies, Parkinson's disease, cancer, and diabetes.
Caffeine is a bitter, white crystalline xanthine alkaloid. It is quickly absorbed through the gastrointestinal tract. It is then metabolized by the liver and through enzymatic action results in three metabolites: paraxanthine, theophylline, and theobromine. It has been shown that elevated levels can appear in the bloodstream within 15 to 45 minutes of consumption, and peak concentrations are evident one hour post ingestion. Circulating concentrations are decreased by 50 to 75% within three to six hours of consumption. Caffeine crosses the membranes of nerve cells as well as muscle cells and it has been proposed that its effects may be more neural than muscular. It has also been proposed that caffeine may have more powerful effects at steps other than metabolism in the process of exciting and contracting the muscle. Research suggests that caffeine acts to decrease reliance on glycogen utilization and increases dependence on free fatty acid mobilization during exercise. It has also been shown that caffeine may improve endurance performance by increasing the secretion of β-endorphins and this may lead to a decrease in pain perception. Other studies indicate that caffeine significantly enhances neuromuscular function and/or skeletal muscle contraction. Caffeine consumption has been shown to promote a significant thermogenic response, namely, increasing energy expended.
Pinitol, a form of Vitamin B inositol, is a plant extract that has insulin-like properties without causing hypoglycemia and stimulates glucose uptake and glycogen synthesis in muscle cells. Chemically, it is defined as an inositol, a kind of sugar alcohol. Enhancing the efficiency of glucose utilization is beneficial as muscle cells more readily uptake glucose and either utilize it for energy or store it as glycogen. Increased glycogen levels in muscles will improve endurance and increase the fullness of muscles. Pinitol stimulates glucose uptake in muscle cells by 25-80%. D-pinitol appears to exert an acute and chronic insulin-like effect in mice that have a hypoinsulinemic type of diabetes. D-pinitol is able to exert this effect independent of insulin, and it appears D-pinitol is able to stimulate glucose transport into the cell via a “by-pass” mechanism that activates the glucose transport cascade distal to the normal activation via the insulin to insulin receptor interaction.
Electrolytes and minerals are crucial to increasing endurance and maintaining the body's physical capabilities during prolonged or highly-intense physical activity. Potassium and magnesium are known to play a major role in overcoming the effects of muscle fatigue. Substantial amounts of potassium and magnesium are lost from the contracting muscles during exercise, and there is a rapid decrease in plasma potassium after the cessation of exercise. A low extracellular potassium concentration can cause muscular weakness, changes in cardiac and kidney function, lethargy and even coma in severe cases. There are no reserves of potassium or sodium in the animal body, and any loss beyond the amount of intake comes from the body's own cells and tissues. The kidney is the key regulator of potassium and sodium. While the kidney can, with a low intake of sodium, reduce excretion thereof to a very low level to conserve the supply in the body, potassium is not so efficiently conserved.
Electrolytes are lost during physical activity through the process of hypotonic dehydration and isotonic dehydration, for example, through sweating or due to high ambient temperatures. The sodium concentration in sweat averages 35 mmol/L, while potassium, calcium and magnesium concentrations in sweat are 5, 1, and 0.8 mmol/L, respectively. Pre-exercise hydration with sodium and other electrolytes has been shown to decrease cardiovascular and thermal strain and enhance exercise capacity in trained and untrained men and women.
There are particular “energy drinks” on the market which purport to increase stamina and physical performance. These beverages generally contain various combinations of caffeine, electrolytes, sugars, juices, herbal extracts, and/or other components which act mainly as stimulants. However, none of these products are specifically designed for enhancing the biogeneration of ATP, nor do they include all the essential components parts of ATP generation or regeneration. Accordingly, there remains a need for a nutraceutical supplement composition which supports a biochemical ready source of cellular energy by promoting the biogeneration of ATP.
Applicants' application Ser. No. 12/911,925, filed on Oct. 26, 2010, is directed to a nutraceutical supplement composition comprising ribose, coenzyme Q10, a saccharide, creatine, and D-pinitol.